Galcanezumab Gets FDA Go-Ahead for Episodic Cluster Headache

Eric Bastings, MD, deputy director of the Division of Neurology Products in the FDA's Center for Drug Evaluation and Research

Eric Bastings, MD

The FDA has approved galcanezumab (Emgality, Eli Lilly) as the first therapy for the treatment of episodic cluster headache in adults. The therapy was approved in its injection formulation, the same for which it was granted approval for preventive migraine treatment in September 2018.¹

In March, galcanezumab, a humanized monoclonal antibody against calcitonin gene-related peptide (CGRP), was designated for priority review by the approving agency.² It was also given a breakthrough therapy label last fall.

“Emgality provides patients with the first FDA-approved drug that reduces the frequency of attacks of episodic cluster headache, an extremely painful and often debilitating condition,” said Eric Bastings, MD, deputy director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research, in an agency statement. “The FDA is committed to continuing to work with drug developers to bring treatments for unmet medical needs to patients.”

The phase 3 trial (NCT02397473) included in the supplemental biologics application (sBLA) evaluated the safety and efficacy of 300-mg galcanezumab in 106 adults with episodic cluster headache. It was one of the first placebo-controlled studies performed in cluster headache, and demonstrated that injections of the study drug resulted in a statistically significant reduction in the frequency of cluster headache attacks compared with placebo (—8.7 reduction for galcanezumab versus a –5.2 reduction for placebo; P =.036) in weeks 1 to 3 of the 2-month study period.

Analysis of the secondary end point, compared at week 3, showed that a significantly greater percentage of patients in the intervention arm (71.4%) achieved a ≥50% reduction in weekly cluster headache attacks compared with placebo (52.6%; P = .046).²

Two galcanezumab-treated patients discontinued double-blind treatment during the episodic cluster headache study due to adverse events (AEs). Overall, the safety profile observed in patients with episodic cluster headache treated with galcanezumab 3000mg monthly is consistent with the safety profile in migraine patients. In data presented at the 2019 American Academy of Neurology Annual Meeting, investigators observed no clinically meaningful differences between the treatment and placebo groups in terms of safety or tolerability, aside from a greater incidence of injection site pain in patients who received galcanezumab versus placebo (8.2% vs 0%; P =.043).³

Eli Lilly is currently enrolling patients for a phase 3b study (NCT02797951) assessing the long-term safety and tolerability of galcanezumab in patients with episodic or chronic cluster headache. Patients that completed the I5Q-MC-CGAL (NCT02397473) or I5Q-MC-CGAM (NCT02438826) phase 3 clinical trials, which evaluated a combined 343 patients and are the largest controlled trials conducted in reducing cluster headache attack frequency, were potentially eligible to enroll. The long-term assessment will evaluate a once-monthly 300-mg dose.

In addition, Eli Lilly is currently recruiting for phase 3 studies evaluating galcanezumab for prevention of migraine in children and adolescents age 6­ to 17.

Jim Martinez, MD, senior medical director, Eli Lilly and Company, previously told NeurologyLive that galcanezumab may provide an option for individuals living with episodic cluster headache, “many of whom may have felt ignored and alone in their struggle.”

“Episodic cluster headache is a severely painful headache disorder that can have a devastating impact on a person’s life,” he explained. “In part, because episodic cluster headache can be difficult to study in clinical trials, there are few treatment options.”

REFERENCES

1. FDA approves first treatment for episodic cluster headache that reduces the frequency of attacks [press release]. Silver Spring, MD: FDA. Published June 4, 2019. fda.gov/news-events/press-announcements/fda-approves-first-treatment-episodic-cluster-headache-reduces-frequency-attacks. Accessed June 4, 2019.

2. Lilly Receives FDA Priority Review Designation for Emgality® (galcanezumab-gnlm) Injection for the Preventive Treatment of Episodic Cluster Headache in Adults [news release]. Indianapolis, IN: Eli Lilly and Company. March 5, 2019. lilly.com/news-releases/news-release-details/lilly-receives-fda-priority-review-designation-emgalityr. Accessed March 5, 2019.

3. Bardos JN, Goadsby PJ, Dodick D, et al. A placebo-controlled study of galcanezumab in patients with episodic cluster headache: results from the 8-week double-blind treatment phase. Presented at: 2019 American Academy of Neurology Annual Meeting. May 4-10, 2019; Philadelphia, PA.